Over the last decade, the Trauma Research Center has explored the role of the gut in the pathogenesis of multiple organ failure (MOF). It is our working hypothesis that the gut is a source of pro-inflammatory mediators in early MOF and serves as a reservoir for pathogens and toxins in late MOF. This research proposal contends that the stomach becomes a reservoir for bacteria during traumatic stress because inhibition of gastric acid secretion occurs with resultant loss of natural bactericidal activity. The inevitable bacterial overgrowth in the stomach may play a significant role in the development of nosocomial pneumonia which occurs in 10%- 65% of IC patients and is associated with case fatality rates ranging from 13-55%. The current research proposal is designed to identify mechanisms regulating inhibition of gastric acid secretion during traumatic stress cause inhibition of gastric acid secretion by the gastric H/K-ATPase, the enzyme responsible for acid secretion, via changes in gut peptide (somatostatin and gastrin) expression which are nitric oxide and prostaglandin sensitive. To address this hypothesis, we will utilize the mesenteric ischemia/reperfusion model as well as the LPD model in rats, because of their abilities to mimic the syndrome of MOF. The specific aims to prove or disprove this hypothesis are as follows. The first aim will be to elucidate the effects of traumatic stress induced experimentally with lipopolysaccharide (LPS( and mesenteric ischemia/reperfusion, on gastric acid secretion. The second aim will evaluate the effects of traumatic stress on the gastric H/K-ATPase. The third aim will determine whether gut peptide (i.e. gastrin and somatostatin) expression is altered following traumatic stress. The fourth aim will examine the role of nitric oxide synthase in traumatic stress induced changes in gastric secretion. The fifth aim will assess whether cyclooxygenase expression modifies gastric secretion following traumatic stress. The results of this research proposal will clarify the mechanisms regulating inhibition of gastric acid secretion during traumatic stress and may allow identification of new therapeutic strategies that could ultimately prevent or decrease the likelihood of developing nosocomial pneumonia in patients with or at high risk for MOF.